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31.
Hydrogen bonds between polarized atoms play a crucial role in protein interactions and are often used in drug design, which usually neglects the potential of C-H...O hydrogen bonds. The 1.4 A resolution crystal structure of the ligand binding domain of the retinoic acid receptor RARgamma complexed with the retinoid SR11254 reveals several types of C-H...O hydrogen bonds. A striking example is the hydroxyl group of the ligand that acts as an H bond donor and acceptor, leading to a synergy between classical and C-H...O hydrogen bonds. This interaction introduces both specificity and affinity within the hydrophobic ligand pocket. The similarity of intraprotein and protein-ligand C-H...O interactions suggests that such bonds should be considered in rational drug design approaches. 相似文献
32.
Hasen KV Samartzis D Casas LA Mustoe TA 《Plastic and reconstructive surgery》2003,112(6):1683-9; discussion 1690-1
The purpose of this study was to determine the differences in measurable outcomes following aesthetic procedures performed under intravenous sedation with incremental doses of midazolam and fentanyl and those performed under propofol infusion. The authors' hypothesis was that the differences in these outcome parameters are not significant between these intravenous sedation protocols. All intraoperative and perioperative records of 84 consecutive patients having aesthetic surgery under a conscious sedation protocol using incremental doses of intravenous midazolam and fentanyl were retrospectively reviewed and compared with the records of a second group of 85 patients having aesthetic surgery under a deep sedation regimen based primarily on propofol infusion. All procedures were hospital based and performed by two surgeons. Twenty-eight different parameters were examined by chart review. In addition, a patient questionnaire was used to assess patient satisfaction and patient recall of operative and perioperative pain, anxiety, nausea, and vomiting. Multivariate statistical analysis was conducted. The two sedation groups were similar with regard to aesthetic procedures performed and patient demographics. The mean duration of operative time was statistically equivalent (152 minutes and 153 minutes). In both groups, there were minor adverse intraoperative events reported but no significant complications. Transient hypotension was more common in the propofol infusion group (12.9 percent versus 2.4 percent, p = 0.018), but no patient required intervention beyond reducing the sedative agent or increasing intravenous fluids. The amount of supplemental fentanyl given intraoperatively was significantly higher in the group whose primary agent for sedation was propofol infusion than the group who received midazolam/fentanyl (209 mug and 143 mug, respectively). The overall questionnaire response rate was 80 percent for both groups. The midazolam/fentanyl sedation group had more recall of "unpleasant intraoperative events" (17 percent versus 3 percent, p = 0.007). However, both groups had low recall of intraoperative pain, anxiety, and nausea. The propofol infusion group experienced significantly more nausea in the recovery room (p = 0.002), nausea at the time of discharge (p = 0.009), and nausea the evening after the operation (p = 0.013). Greater than 90 percent of the patients in both groups would have the same anesthetic in the future rather than undergo general anesthesia. Patient safety, outcomes, and satisfaction are similar in plastic surgery procedures performed under sedation protocols using either incremental doses of midazolam and fentanyl or propofol infusion. All operative and postoperative outcomes for pain, anxiety, and vomiting were similar in the two groups except for immediate postoperative nausea, which was higher in the propofol infusion group. The overall satisfaction of patients undergoing plastic surgery procedures under these intravenous sedation protocols appears very high. 相似文献
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With warmer weather projections, workplace heat exposure is presenting a growing challenge to workers’ health and safety. Occupational hygienists are the specialist group conducting measurements and providing advice on heat stress management to industry. In order to provide insights into hygienists perceptions on workplace heat exposure, current and future preparedness for extreme heat, and barriers to possible heat adaptation strategies, a self-administered questionnaire survey was conducted during a national conference of the Australian Institute of Occupational Hygienists. Nearly 90% of the 180 respondents were at least moderately concerned about extreme heat and 19% were dissatisfied with current heat stress prevention measures. Barriers recognized by the participants were lack of awareness (68%), insufficient training (56%), unsatisfactory management commitment (52%), and low compliance with prevention policies (40%). The findings suggest a need to refine occupational heat management and prevention strategies. 相似文献
35.
36.
The identification of a series of novel, soluble non-peptidic neuropeptide Y Y2 receptor antagonists
Lunniss GE Barnes AA Barton N Biagetti M Bianchi F Blowers SM Caberlotto LL Emmons A Holmes IP Montanari D Norris R Puckey GV Walters DJ Watson SP Willis J 《Bioorganic & medicinal chemistry letters》2010,20(24):7341-7344
The identification and subsequent optimisation of a selective non-peptidic NPY Y2 antagonist series is described. This led to the development of amine 2, a selective, soluble NPY Y2 receptor antagonist with enhanced CNS exposure. 相似文献
37.
Ana Paula M. Bernardi Natasha Maurmann Sandra B. Rech Gilsane von Poser 《Acta Physiologiae Plantarum》2007,29(2):165-170
Hypericum polyanthemum Klotzsch ex Reichardt, an endemic species of Southern Brazil, was micropropagated on MS medium supplemented with 1.78 μM
BAP. Shoot proliferation and rooting was achieved on hormone-free medium and plantlets survived acclimatization. The bioactive
compounds: 6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran (HP1), 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran
(HP2) and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran (HP3) were quantified in the leaves, stems and roots of
propagated and acclimatized plantlets and compared with the field-grown plants. The HPLC analysis revealed that the three
benzopyrans are accumulated in the aerial parts and the concentration varied with the age of the plant whereas the roots were
capable of accumulating only HP3. Greatest yield of HP1 (7.12 mg/g DW) was quantified in the leaves of the acclimatized plantlets,
whereas the flowers of the plants from natural habitat displayed higher amounts of HP2 (11.04 mg/g DW) and HP3 (13.99 mg/g
DW). 相似文献
38.
Engelmann FM Mayer I Gabrielli DS Toma HE Kowaltowski AJ Araki K Baptista MS 《Journal of bioenergetics and biomembranes》2007,39(2):175-185
Two series of cationic porphyrins meso-(3N-methylpyridinium)phenylporphyrin (3P1, 3P2c, 3P2t, 3P3 and 3P4) and meso-(4N-methylpyridinium)phenylporphyrin (4P1, 4P2c, 4P2t, 4P3 and 4P4) were studied to obtain a comprehensive understanding of factors
that influence the binding of cationic porphyrins to liposomes and mitochondria, as well as their photodynamic efficiencies
in erythrocytes. Binding and photodynamic efficiency were found to be inversely proportional to the number of positively charged
groups and directly proportional to n-octanol/water partition coefficients (log POW), except for the cis molecules 3P2c and 4P2c. In the cis molecules, binding and photodynamic efficiency were much higher than expected, indicating that specific interactions not
accounted by log POW enhance photodynamic efficiency. The effect of mitochondrial transmembrane electrochemical potentials on cationic porphyrin
binding constants was estimated to be as large as 15%, and may be useful to selectively target this organelle when promoting
photodynamic therapy to induce apoptosis. 相似文献
39.
Mutagenic and carcinogenic potential of a textile azo dye processing plant effluent that impacts a drinking water source 总被引:4,自引:0,他引:4
Alves de Lima RO Bazo AP Salvadori DM Rech CM de Palma Oliveira D de Aragão Umbuzeiro G 《Mutation research》2007,626(1-2):53-60
Recently a textile azo dye processing plant effluent was identified as one of the sources of mutagenic activity detected in the Cristais River, a drinking water source in Brazil [G.A. Umbuzeiro, D.A. Roubicek, C.M. Rech, M.I.Z. Sato, L.D. Claxton, Investigating the sources of the mutagenic activity found in a river using the Salmonella assay and different water extraction procedures, Chemosphere 54 (2004) 1589-1597]. Besides presenting high mutagenic activity in the Salmonella/microsome assay, the mutagenic nitro-aminoazobenzenes dyes CI Disperse Blue 373, CI Disperse Violet 93, and CI Disperse Orange 37 [G.A. Umbuzeiro, H.S. Freeman, S.H. Warren, D.P. Oliveira, Y. Terao, T. Watanabe, L.D. Claxton, The contribution of azo dyes in the mutagenic activity of the Cristais river, Chemosphere 60 (2005) 55-64] as well as benzidine, a known carcinogenic compound [T.M. Mazzo, A.A. Saczk, G.A. Umbuzeiro, M.V.B. Zanoni, Analysis of aromatic amines in surface waters receiving wastewater from textile industry by liquid chromatographic with eletrochemical detection, Anal. Lett., in press] were found in this effluent. After approximately 6 km from the discharge of this effluent, a drinking water treatment plant treats and distributes the water to a population of approximate 60,000. As shown previously, the mutagens in the DWTP intake water are not completely removed by the treatment. The water used for human consumption presented mutagenic activity related to nitro-aromatics and aromatic amines compounds probably derived from the cited textile processing plant effluent discharge [G.A. Umbuzeiro, D.A. Roubicek, C.M. Rech, M.I.Z. Sato, L.D. Claxton, Investigating the sources of the mutagenic activity found in a river using the Salmonella assay and different water extraction procedures, Chemosphere 54 (2004) 1589-1597; G.A. Umbuzeiro, H.S. Freeman, S.H. Warren, D.P. Oliveira, Y. Terao, T. Watanabe, L.D. Claxton, The contribution of azo dyes in the mutagenic activity of the Cristais river, Chemosphere 60 (2005) 55-64]. Therefore, it is important to evaluate the possible risks involved in the human consumption of this contaminated water. With that objective, one sample of the cited industrial effluent was tested for carcinogenicity in the aberrant crypt foci medium-term assay in colon of Wistar rats. The rats received the effluent in natura through drinking water at concentrations of 0.1%, 1%, and 10%. The effluent mutagenicity was also confirmed in the Salmonella/microsome assay with the strains TA98 and YG1041. There was an increased number of preneoplastic lesions in the colon of rats exposed to concentrations of 1% and 10% of the effluent, and a positive response for both Salmonella strains tested. These results indicate that the discharge of the effluent should be avoided in waters used for human consumption and show the sensitivity of the ACF crypt foci assay as an important tool to evaluate the carcinogenic potential of environmental complex mixtures. 相似文献
40.